Synthetic peptides and methods of use for autoimmune disease therapies

Abstract

The invention provides peptide compositions, and methods of making and using therapeutic compositions for treatment of a subject for an autoimmune or an inflammatory disease. The invention also provides kits for assaying binding of a composition to a water-soluble MHC protein.

1. An isolated synthetic peptide having a sequence selected from the group consisting of: AKEYAAAAAAKAAAA (SEQ ID NO: 7), AAEYAAAAAAKAAAA (SEQ ID NO: 12), AAKYAEAAAAKAAAA (SEQ ID NO: 15), and EAKYAAAAAAKAAAA (SEQ ID NO: 18), wherein the synthetic peptide binds to an MHC class II protein with higher affinity than a control peptide CII 261-273 (SEQ ID NO: 2) or HA 306-318 (SEQ ID NO: 1). 
     
     
       2. The isolated peptide according to any of the peptides of  claim 1 , in which the tyrosine (Y) has been substituted by a valine (V) or a phenylalanine (F), wherein the peptide has an amino acid sequence selected from the group of: AKEVAAAAAAKAAAA (SEQ ID NO: 61), AAEVAAAAAAKAAAA (SEQ ID NO: 62), AAKVAPAAAAKAAAA (SEQ ID NO: 63), and EAKVAAAAAAKAAAA (SEQ ID NO: 64) AKEFAAAAAAKAAAA (SEQ ID NO: 65), AAEFAAAAAAKAAAA (SEQ ID NO: 66), AAKFAEAAAAKAAAA (SEQ ID NO: 67), and EAKFAAAAAAKAAAA (SEQ ID NO: 68). 
     
     
       3. An isolated synthetic peptide having a sequence selected from the group consisting of: AEKYAAAAAAKAAAA (SEQ ID NO: 6), AKEYAAAAAAKAAAA (SEQ ID NO: 7), KEAYAAAAAAKAAAA (SEQ ID NO: 10), AEEYAAAAAAKAAAA (SEQ ID NO: 11), AAEYAAAAAAKAAAA (SEQ ID NO: 12), EKAYAAAAAAKAAAA (SEQ ID NO: 13), AAKYEAAAAAKAAAA (SEQ ID NO: 14), AAKYAEAAAAKAAAA (SEQ ID NO: 15), EAAYAAAAAAKAAAA (SEQ ID NO: 16), EKKYAAAAAAKAAAA (SEQ ID NO: 17), EAKYAAAAAAKAAAA (SEQ ID NO: 18), AKKYEAAAAAAAAAA (SEQ ID NO: 21), AAEYKAAAAAAAAAA (SEQ ID NO: 26), AAKYEAAAAAAAAAA (SEQ ID NO: 28), AAKYAEAAAAAAAAA (SEQ ID NO: 29), AEYAKAAAAAAAAAA (SEQ ID NO: 32), AEKAYAAAAAAAAAA (SEQ ID NO: 33), AYKAEAAAAAAAAAA (SEQ ID NO: 35), and AKYAEAAAAAAAAAA (SEQ ID NO: 36), wherein the synthetic peptide binds to an MHC class II protein with higher affinity than a control peptide CII 261-273 (SEQ ID NO: 2) or HA 306-318 (SEQ ID NO: 1). 
     
     
       4. The isolated peptide according to any of the sequences of  claim 3 , in which the tyrosine (Y) has been substituted by a valine (V) or a phenylalanine (F), wherein the peptide has an amino acid sequence selected from the group of: AEKVAAAAAAKAAAA (SEQ ID NO: 69), AKEVAAAAAAKAAAA (SEQ ID NO: 70), KEAVAAAAAAKAAAA (SEQ ID NO: 71), AEEVAAAAAAKAAAA (SEQ ID NO: 72), AAEVAAAAAAKAAAA (SEQ ID NO: 73), EKAVAAAAAAKAAAA (SEQ ID NO: 74), AAKVEAAAAAKAAAA (SEQ ID NO: 75), AAKVAEAAAAKAAAA (SEQ ID NO: 76), EAAVAAAAAKAAAA (SEQ ID NO: 77), EKKVAAAAAAKAAAA (SEQ ID NO: 78), EAKVAAAAAAKAAAA (SEQ ID NO: 79), AKKVEAAAAAAAAAA (SEQ ID NO: 80), AAEVKAAAAAAAAAA (SEQ ID NO: 81), AAKVEAAAAAAAAAA (SEQ ID NO: 82), AAKVAEAAAAAAAAA (SEQ ID NO: 83), AEVAKAAAAAAAAAA (SEQ ID NO: 84), AEKAVAAAAAAAAAA (SEQ ID NO: 85), AVKAEAAAAAAAAAA (SEQ ID NO: 86), AKVAEAAAAAAAAAA (SEQ ID NO: 87), AEKFAAAAAAKAAAA (SEQ ID NO: 88), AKEFAAAAAAKAAAA (SEQ ID NO: 89), KEAFAAAAAAKAAAA (SEQ ID NO: 90), AEEFAAAAAAKAAAA (SEQ ID NO: 91), AAEFAAAAAAKAAAA (SEQ ID NO: 92), EKAFAAAAAAKAAAA (SEQ ID NO: 93), AAKFEAAAAAKAAAA (SEQ ID NO: 94), AAKFAEAAAAKAAAA (SEQ ID NO: 95), EAAFAAAAAAKAAAA (SEQ ID NO: 96), EKKFAAAAAAKAAAA (SEQ ID NO: 97), EAKFAAAAAAKAAAA (SEQ ID NO: 98), AKKFEAAAAAAAAAA (SEQ ID NO: 99), AAEFKAAAAAAAAAA (SEQ ID NO: 100), AAKFEAAAAAAAAAA (SEQ ID NO: 101), AAKFAEAAAAAAAAA (SEQ ID NO: 102), AEFAKAAAAAAAAAA (SEQ ID NO: 103), AEKAFAAAAAAAAAA (SEQ ID NO: 104), AFKAEAAAAAAAAAA (SEQ ID NO: 105), and AKFAEAAAAAAAAAA (SEQ ID NO: 106).